Spinophilin is required for normal morphology, Ca(2+) homeostasis and contraction but dispensable for β-adrenergic stimulation of adult cardiomyocytes.

Spinophilin (SPN) is a ubiquitously expressed scaffolding protein that interacts through several binding modules with a variety of target proteins. Thus, SPN bundles F-actin, targets protein phosphatase 1 to the ryanodine receptor, and targets regulators of G-protein signaling to G-protein coupled receptors in cardiomyocytes. In this work we studied the role of SPN on cardiomyocyte morphology, function, and β-adrenergic responsiveness using a homozygous SPN knock-out mouse model (SPN−/−). We show that spinophilin deficiency significantly (1) reduced cardiomyocyte length, (2) increases both Ca2+ amplitude and maximal rate of Ca2+ rise during systole, and (3) decreased shortening amplitude and maximal rate of shortening, while (4) β-adrenergic stimulation remained intact. Our data suggest that spinophilin is an upstream regulator required for normal growth and excitation–contraction coupling, but is dispensable for β-adrenergic stimulation of adult cardiomyocytes.